Responses to angiotensin peptides are mediated by AT1 receptors in the rat.
The effects of the angiotensin AT1 and AT2 receptor antagonists candesartan and PD-123,319 on hemodynamic responses to angiotensin peptides were investigated in the anesthetized rat. Injections of angiotensin II and III caused dose-related increases in systemic arterial and in hindquarters perfusion pressure that were reduced in an insurmountable manner by candesartan. Pressor responses to angiotensin IV were also attenuated, and a vasodepressor or vasodilator response to the angiotensin peptides was not unmasked by the AT1 receptor antagonists candesartan or losartan. The AT2 receptor antagonist PD-123,319 had no significant effect on increases in systemic arterial and hindquarters perfusion pressure in response to the angiotensin peptides. Pressor responses to angiotensin peptides were not altered by adrenergic nerve terminal and alpha-receptor blocking agents or by the cyclooxygenase inhibitor sodium meclofenamate but were increased by an inhibitor of nitric oxide synthase. The present results suggest that pressor responses to the angiotensin peptides are mediated by the activation of AT1 receptors and that AT2 receptors, the adrenergic system, or cyclooxygenase products do not appear to modulate hemodynamic responses to the angiotensin peptides in the anesthetized rat.
Champion
H C
HC
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Czapla
M A
MA
Kadowitz
P J
PJ
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology*; D000805:Angiotensin III / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D000805:Angiotensin III; C073402:PD 123319; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D019808:Losartan; C081643:candesartan; D009638:Norepinephrine